Effects of synthetic gestagens on fish reproduction

Abstract

Abstract-Although it is well known that estrogenic steroidal hormones are able to affect the sexual development and reproduction of fish at low concentrations, no data on environmental effects of the class of progestogenic hormones are available yet. Synthetic gestagens (progestins) are a component in oral contraceptives. Upon their use, a fraction of the progestins will be excreted via urine into the aquatic environment. On the basis of their pharmacological action in mammals, it is supposed that fish reproduction is the most sensitive endpoint for the progestin treatment. In order to test this assumption, the effects of two progestins currently marketed in contraceptive formulations, levonorgestrel (LNG) and drospirenone (DRSP), were investigated in adult fathead minnows (Pimephales promelas) following an Organization for Economic Cooperation and Development 21-d fish reproduction screening assay draft protocol with additional end points. Levonorgestrel was tested at measured concentrations of 0.8, 3.3, and 29.6 ng/L, and DRSP at concentrations of 0.66, 6.5, and 70 mg/L. Both tested progestins caused an inhibition of reproduction. For LNG, this occurred at concentrations of $0.8 ng/L, no no-observed-effect concentration (NOEC) could be defined. Higher concentrations resulted in masculinization of females with de novo synthesis of nuptial tubercles. Drospirenone treatment, however, affected the reproductive success of fathead minnow at concentrations of 6.5 mg/L and higher with a clear dose-response relationship and a NOEC of 0.66 mg/L, which is above environmentally relevant concentrations.

The progestin levonorgestrel affects sex differentiation in zebrafish at environmentally relevant concentrations

“…In agreement with this, strong androgenic effects of LNG were also observed in three-spined sticklebacks (Gasterosteus aculeatus), including the induction of a male specific glue protein, called spiggin, at concentrations ≥40 ng/L, and the disruption of the androgen-dependent reproductive cycle in males at concentrations ≥6.5 ng/L (Svensson et al, 2013(Svensson et al, , 2014. Exposure of fathead minnows (Pimephales promelas) to LNG (29.6 ng/L) resulted in the masculinization of female secondary sex characteristics (Zeilinger et al, 2009). …”

“…Progestins (also called progestogens) are synthetic pharmaceutical compounds that are commonly used in contraception and hormone replacement therapies (Zeilinger et al, 2009). Similar to estrogens and androgens, progestins can enter the aquatic environment through wastewater treatment plant effluents, and pastoral agricultural runoff (Chang et al, 2009;Mansell et al, 2011).…”

“…Although environmental concentrations of progestins are generally only measured at up to tens of ng/L in surface water and hundreds of ng/L in sewage treatment plant effluents (Liu et al, 2011a), the progestins generally display high potency and specificity for biological targets (Fick et al, 2010), many of which are highly conserved between species (Gunnarsson et al, 2008). Recently, there has been a growing concern of the potential adverse impacts that Zeilinger et al, 2009) and amphibians (Hoffmann and Kloas, 2012;Kvarnryd et al, 2011;Lorenz et al, 2011;Säfholm et al, 2011) at low ng/L concentrations. A recent study with three-spined stickleback showed strong androgenic effects on the reproductive cycle in females (Svensson et al, 2013) and disruption of the androgen-dependent reproductive cycle in males (Svensson et al, 2014).…”

Effect of combined exposure to lead and decabromodiphenyl ether on neurodevelopment of zebrafish larvae

“…Measured actual concentrations of BDE-209 in water were decreased relative to the nominal concentrations of the treatment groups (about 20% decrease; supplementary data Table S3). This could be due to BDE-209 sorption to tank, fish, and water particulates, or degradation during the exposure period (Zeilinger et al, 2009).…”

Analysis of 21 progestagens in various matrices by ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) with diverse sample pretreatment

“…Previous environmental studies about steroid hormones mostly focused on estrogens [4][5][6][7] and a few studies on other steroids such as progestagens [8][9][10][11]. It is now well established that various natural and synthetic progestagens are widely used in humans and animals daily life for many reasons [12,13], and recent studies have shown the reproductive toxicity of progestagens to aquatic organisms at nanograms per liter levels [14][15][16][17][18][19]. Therefore, the presence of progestogens in the environment should deserve greater attention, and it is essential to develop sensitive and reliable analytical methods for determination of the broad number of progestagens in various environmental matrices in order to assess their environmental risks.…”